A major objective is the determination of a thermal denaturation (thermal dispersion) map of lambda DNA by high resolution solution methods. Specific aims involve the thermal dispersion of DNA, the development of explicit theoretical models for intermediates during denaturation, and the application of these developments to the thermal denaturation of lambda DNA. Methodological aims include the development of analytical techniques to be applied to high resoultion thermal dispersion curves of DNA, and include (1) reconstruction of a derivative profile from the experimental differential, (2) deconvolution of complex denaturation profiles into discrete subtransitions, and (3) the determination of the fractional G C basecomposition, the size (in base pairs) and the locus in the DNA of sequence domains that denature as determined by the effects of specific cleavage with restriction enzymes on high resolution melting curves and by two-dimensional formamide gradient, denaturation gel s electrophoresis of randomly sheared fragments. A second major objective involves a quantitative analysis of the long range destabilizing effects of phosphate-phosphate interactions in lambda DNA from the effects of the sodium counterion concentration on the high resolution denaturation pattern of lambda DNA. A third major objective involves the further physical characterization of repetitive sequence groups in bovine DNA according to their precise number, length, base composition, overall sequence divergence, local sequence divergence, and fraction of the total genomic DNA. A fourth specific aim is to determine the range and magnitude of the energetic effects of UV photo-induced thymine dimers on the stability of neighboring segments in phi x-174 RF Form II DNA, from a systematic analysis of high resolution melting profiles.